TY - JOUR
T1 - Two truncating variants in FANCC and breast cancer risk
AU - ABCTB Investigators
AU - NBCS Collaborators
AU - Dörk, Thilo
AU - Peterlongo, Paolo
AU - Mannermaa, Arto
AU - Bolla, Manjeet K.
AU - Wang, Qin
AU - Dennis, Joe
AU - Ahearn, Thomas
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Arndt, Volker
AU - Aronson, Kristan J.
AU - Augustinsson, Annelie
AU - Freeman, Laura E.Beane
AU - Beckmann, Matthias W.
AU - Beeghly-Fadiel, Alicia
AU - Behrens, Sabine
AU - Bermisheva, Marina
AU - Blomqvist, Carl
AU - Bogdanova, Natalia V.
AU - Bojesen, Stig E.
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Burwinkel, Barbara
AU - Canzian, Federico
AU - Chan, Tsun L.
AU - Chang-Claude, Jenny
AU - Chanock, Stephen J.
AU - Choi, Ji Yeob
AU - Christiansen, Hans
AU - Clarke, Christine L.
AU - Couch, Fergus J.
AU - Czene, Kamila
AU - Daly, Mary B.
AU - dos-Santos-Silva, Isabel
AU - Dwek, Miriam
AU - Eccles, Diana M.
AU - Ekici, Arif B.
AU - Eriksson, Mikael
AU - Evans, D. Gareth
AU - Fasching, Peter A.
AU - Figueroa, Jonine
AU - Flyger, Henrik
AU - Fritschi, Lin
AU - Gabrielson, Marike
AU - Gago-Dominguez, Manuela
AU - Gao, Chi
AU - Gapstur, Susan M.
AU - García-Closas, Montserrat
AU - García-Sáenz, José A.
AU - Gaudet, Mia M.
AU - Giles, Graham G.
AU - Goldberg, Mark S.
AU - Goldgar, David E.
AU - Guénel, Pascal
AU - Haeberle, Lothar
AU - Haiman, Christopher A.
AU - Håkansson, Niclas
AU - Hall, Per
AU - Hamann, Ute
AU - Hartman, Mikael
AU - Hauke, Jan
AU - Hein, Alexander
AU - Hillemanns, Peter
AU - Hogervorst, Frans B.L.
AU - Hooning, Maartje J.
AU - Hopper, John L.
AU - Howell, Tony
AU - Huo, Dezheng
AU - Ito, Hidemi
AU - Iwasaki, Motoki
AU - Jakubowska, Anna
AU - Janni, Wolfgang
AU - John, Esther M.
AU - Jung, Audrey
AU - Kaaks, Rudolf
AU - Kang, Daehee
AU - Kapoor, Pooja Middha
AU - Khusnutdinova, Elza
AU - Kim, Sung Won
AU - Kitahara, Cari M.
AU - Koutros, Stella
AU - Kraft, Peter
AU - Kristensen, Vessela N.
AU - Kwong, Ava
AU - Lambrechts, Diether
AU - Marchand, Loic Le
AU - Li, Jingmei
AU - Lindström, Sara
AU - Linet, Martha
AU - Lo, Wing Yee
AU - Long, Jirong
AU - Lophatananon, Artitaya
AU - Lubiński, Jan
AU - Manoochehri, Mehdi
AU - Manoukian, Siranoush
AU - Margolin, Sara
AU - Martinez, Elena
AU - Matsuo, Keitaro
AU - Mavroudis, Dimitris
AU - Meindl, Alfons
AU - Menon, Usha
AU - Milne, Roger L.
AU - Mohd Taib, Nur Aishah
AU - Muir, Kenneth
AU - Mulligan, Anna Marie
AU - Neuhausen, Susan L.
AU - Nevanlinna, Heli
AU - Neven, Patrick
AU - Newman, William G.
AU - Offit, Kenneth
AU - Olopade, Olufunmilayo I.
AU - Olshan, Andrew F.
AU - Olson, Janet E.
AU - Olsson, Håkan
AU - Park, Sue K.
AU - Park-Simon, Tjoung Won
AU - Peto, Julian
AU - Plaseska-Karanfilska, Dijana
AU - Pohl-Rescigno, Esther
AU - Presneau, Nadege
AU - Rack, Brigitte
AU - Radice, Paolo
AU - Rashid, Muhammad U.
AU - Rennert, Gad
AU - Rennert, Hedy S.
AU - Romero, Atocha
AU - Ruebner, Matthias
AU - Saloustros, Emmanouil
AU - Schmidt, Marjanka K.
AU - Schmutzler, Rita K.
AU - Schneider, Michael O.
AU - Schoemaker, Minouk J.
AU - Scott, Christopher
AU - Shen, Chen Yang
AU - Shu, Xiao Ou
AU - Simard, Jacques
AU - Slager, Susan
AU - Smichkoska, Snezhana
AU - Southey, Melissa C.
AU - Spinelli, John J.
AU - Stone, Jennifer
AU - Surowy, Harald
AU - Swerdlow, Anthony J.
AU - Tamimi, Rulla M.
AU - Tapper, William J.
AU - Teo, Soo H.
AU - Terry, Mary Beth
AU - Toland, Amanda E.
AU - Tollenaar, Rob A.E.M.
AU - Torres, Diana
AU - Torres-Mejía, Gabriela
AU - Troester, Melissa A.
AU - Truong, Thérèse
AU - Tsugane, Shoichiro
AU - Untch, Michael
AU - Vachon, Celine M.
AU - Ouweland, Ans M.W.van den
AU - Veen, Elke M.van
AU - Vijai, Joseph
AU - Wendt, Camilla
AU - Wolk, Alicja
AU - Yu, Jyh Cherng
AU - Zheng, Wei
AU - Ziogas, Argyrios
AU - Ziv, Elad
AU - Balleine, Rosemary
AU - Baxter, Robert
AU - Braye, Stephen
AU - Carpenter, Jane
AU - Dahlstrom, Jane
AU - Forbes, John
AU - Lee, C. Soon
AU - Marsh, Deborah
AU - Morey, Adrienne
AU - Pathmanathan, Nirmala
AU - Scott, Rodney
AU - Simpson, Peter
AU - Spigelman, Allan
AU - Wilcken, Nicholas
AU - Yip, Desmond
AU - Zeps, Nikolajs
AU - Børresen-Dale, Anne Lise
AU - Grenaker Alnæs, Grethe I.
AU - Sahlberg, Kristine K.
AU - Ottestad, Lars
AU - Kåresen, Rolf
AU - Schlichting, Ellen
AU - Holmen, Marit Muri
AU - Sauer, Toril
AU - Haakensen, Vilde
AU - Engebråten, Olav
AU - Naume, Bjørn
AU - Fosså, Alexander
AU - Kiserud, Cecile E.
AU - Reinertsen, Kristin V.
AU - Helland, Åslaug
AU - Riis, Margit
AU - Geisler, Jürgen
AU - Dunning, Alison M.
AU - Pharoah, Paul D.P.
AU - Schindler, Detlev
AU - Devilee, Peter
AU - Easton, Douglas F.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
AB - Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
UR - http://www.scopus.com/inward/record.url?scp=85071631153&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-48804-y
DO - 10.1038/s41598-019-48804-y
M3 - Article
C2 - 31467304
AN - SCOPUS:85071631153
SN - 2045-2322
VL - 9
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 12524
ER -